In a randomized, double-blind, double-dummy, cross-over study the efficacy and safety of inhaled salmeterol 50 mcg (b.i.d.) was compared with oral salbutamol controlled release 8 mg (b.i.d.). Fifty-nine patients with moderate asthma were randomized to two four-week periods of treatment with a two-week washout period. During the study period the patients were allowed to use inhaled Salbutamol on a prn. basis. Inhaled steroids, if any, were continued. On diary cards patients recorded peak expiratory flow rate (PEFR) morning and evening before medication, asthma symptom score, and use of inhaled salbutamol. Salmeterol was more effective than salbutamol CR in decreasing daily symptoms (p = 0.001) and increasing morning-PEFR (p = 0.004). Salmeterol resulted in significantly more days without symptoms (p = 0.0004) and days and nights without need for rescue medication (p = 0.01 and p = 0.01). Salmeterol was better tolerated than salbutamol CR.